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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease

When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

Parsons-Wingerter, Patricia↗
NASA NTRS1975

Applications of Doppler ultrasound in clinical vascular disease

Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

Barnes, R. W.↗
NASA NTRS2007

Triamcinolone Acetonide Selectively Inhibits Angiogenesis in Small Blood Vessels and Decreases Vessel Diameter within the Vascular Tree

The steroid triamcinolone acetonide (TA) is a potent anti-angiogenesis drug used to treat retinal vascular diseases that include diabetic retinopathy, vascular occlusions and choroidal neovascularization. To quantify the effects of TA on branching morphology within the angiogenic microvascular tree of the chorioallantoic membrane (CAM) of quail embryos. Increasing concentrations of TA (0-16 ng/ml) were applied topically on embryonic day 7 (E7) to the chorioallantoic membrane (CAM) of quail embryos cultured in Petri dishes, and incubated for an additional 24 or 48 hours until fixation. Binary (black/white) microscopic images of arterial end points were quantified by VESGEN software (for Generational Analysis of Vessel Branching) to obtain major vascular parameters that include vessel diameter (Dv), fractal dimension (Df), tortuosity (Tv) and densities of vessel area, length, number and branch point (Av, Lv, Nv and Brv). For assessment of specific changes in vascular morphology induced by TA, the VESGEN software automatically segmented the vascular tree into branching generations (G1...G10) according to changes in vessel diameter and branching. Vessel density decreased significantly up to 34% as the function of increasing concentration of TA according to Av, Lv, Brv, Nv and Df. TA selectively inhibited the growth of new, small vessels, because Lv decreased from 13.14plus or minus 0.61 cm/cm2 for controls to 8.012 plus or minus 0.82 cm/cm2 at 16 ng TA/ml in smaller branching generations (G7-G10), and for Nv from 473.83 plus or minus 29.85 cm(-)2 to 302.32 plus or minus 33.09 cm-()2. In contrast, vessel diameter (Dv) decreased throughout the vascular tree (G1-G10).

McKay, Terri L.↗
NASA NTRS2014

Mapping by VESGEN of Blood Vessels in the Retinas of ISS Crew Members and Bed Rest Subjects for Increased Understanding of VIIP

Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy.

ISS Crew↗
NASA NTRS2017

Mapping by VESGEN of Blood Vessels in the Retinas of Astronauts Pre- and Post-Flight to the ISS

Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.

VESGEN↗
NASA NTRS2018

Differences in Pre and Post Vascular Patterning Within Retinas from ISS Crew Members and Head-Down Tilt (HDT) Subjects by VESGEN Analysis

Accelerated research by NASA has investigated the significant risks incurred during long-duration missions in microgravity for Space Flight-Associated Neuro-ocular Syndrome (SANS, formerly known as Visual Impairments associated with Increased Intracranial Pressure, VIIP) [1]. For our study, NASA's VESsel GENeration Analysis (VESGEN) was used to investigate the role of retinal blood vessels in the etiology of SANS/VIIP. The response of retinal vessels to microgravity was evaluated in astronaut crew members pre and post flight to the International Space Station (ISS), and compared to the response of retinal vessels in healthy volunteers to 6deg head-down tilt during 70 days of bed rest (HDTBR). For the study, we are testing the hypothesis that long-term cephalad fluid shifts resulting in ocular and visual impairments are necessarily mediated in part by retinal blood vessels, and therefore are accompanied by structural adaptations of the vessels. METHODS: Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30deg infrared (IR) Heidelberg Spectralis images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). VESGEN is a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues. The multi-parametric VESGEN analysis generates maps of branching arterial and venous trees quantified by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations according to vascular physiological branching rules. The retrospective study approved by NASA's Institutional Review Board included the analysis of bilateral retinas in eight ISS crew members monitored by routine occupational surveillance and six HDTBR subjects (NASA FARU Campaign 11, for example). The VESGEN analysis was conducted in a blinded fashion, with IR retinal images masked to the subject's identity, ophthalmic and clinical characteristics, and to the temporal sequence of image collection. To complete our study, VESGEN results will be analyzed statistically and correlated with other ophthalmic and medical findings. RESULTS: Preliminary results for changes in the pre to post status of vascular patterning in the retinas of crew members and HDTBR subjects are interestingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in the majority of crew members (11/16 retinas). In contrast, vascular densities increased in HDTBR subjects by the same parameters (6/10 retinas). To conclude the study, biostatistics and medical analyses will be conducted to quantify and draw conclusions about how the changes associated with flight compare to those associated with HDTBR. CONCLUSIONS: Vascular densities appeared to decrease in the retinas of ISS crew members and increase in HDTBR subjects. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDTBR may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70 days HDTBR), or the presence of gravity in HDTBR compared to microgravity on the ISS. In addition, increased and decreased vessel diameters for Crew Members and HDTBR, respectively, are subject to limits of im

Vascular↗
NASA NTRS2018

Differences in Pre and Post Vascular Patterning of Retinas from ISS Crew Members and HDT Subjects by VESGEN Analysis

Accelerated research by NASA [1] has investigated the significant risks for visual and ocular impairments Spaceflight Associated Neuro-Ocular Syndrome /Visual Impairment/Intracranial Pressure (SANS/VIIP) incurred by microgravity spaceflight, especially long-duration missions. Our study investigates the role of blood vessels in the incidence and etiology of SANS/VIIP within the retinas of Astronaut crewmembers pre-and post-flight to the International Space Station (ISS) by NASA's VESsel GENeration Analysis (VESGEN). The response of retinal vessels in crewmembers to microgravity was compared to that of retinal vessels to Head-Down Tilt (HDT) in subjects undergoing 70-Day Bed Rest. The study tests the proposed hypothesis that cephalad fluid shifts missions, resulting in ocular and visual impairments, are necessarily mediated in part by retinal blood vessels, and are therefore accompanied by significant remodeling of retinal vasculature.Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30° infrared (IR) Heidelberg Spectralis® images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues [2]. The weighted, multi-parametric VESGEN analysis generates maps of branching arterial and venous trees and quantification by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations by vascular physiological branching rules [2,3]. The retrospective study approved by NASA’s Institutional Review Board included six HDT subjects (NASA Flight Analogs Research Unit [FARU] Campaign 11; for example, [4]) and eight ISS crewmembers monitored by routine occupational surveillance who provided their study consents to NASA’s Lifetime Surveillance of Astronaut Health (LSAH). For the initial blinded VESGEN phase, ophthalmic retinal images were masked as to subject identity and pre- and post-status. In the second unblinded phase, VESGEN results were analyzed according to the pre- and post-status of left and right retinas matched to each subject. To complete our study, vascular results will be subjected to NASA biostatistical analysis and correlated with other ophthalmic and medical findings. Preliminary results for changes in the pre- to post-status of vascular patterning in the retinas of crewmembers and HDT subjects are strikingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in a substantial subset of crewmembers (11/16 retinas). In contrast, vascular densities increased in a substantial subset of HDT subjects by the same parameters (6/10 retinas, currently excluding one anomalous subject). To conclude the study, biostatistical and medical analyses will be of critical importance for investigating the validity of these vascular findings. Vascular densities appeared to decrease in the retinas of crewmembers following ISS Missions, and increase in subjects after HDT. The vascular increases and decreases most likely derive primarily from limits of resolution to the ophthalmic imaging that does not capture the smallest vessels, rather than from vessel growth or atrophy. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDT may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70-day HDT), or the presence of gravity in HDT compared to microgravity onboard the ISS. To conclude our study, the biostatistical and medical analyses will be of critical importance for investigating the validity and significance of the VESGEN findings.

Murray, M. C.↗
NASA NTRS2001

Shear stress reduces protease activated receptor-1 expression in human endothelial cells

Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.

Non-NASA Center↗
NASA NTRS1988

Serotonin, atherosclerosis, and collateral vessel spasm

Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.

Review, Tutorial↗
NASA NTRS2006

Stress, and pathogen response gene expression in modeled microgravity

Purpose: Immune suppression in microgravity has been well documented. With the advent of human exploration and long-term space travel, the immune system of the astronaut must be optimally maintained. It is important to investigate the expression patterns of cytokine genes, because they are directly related to immune response. Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in the cells of every life form. These proteins are induced when a cell responds to stressors such as heat, cold and oxygen deprivation. Microgravity is another stressor that may regulate HSPs. Heat shock proteins trigger immune response through activities that occur both inside the cell (intracellular) and outside the cell (extracellular). Knowledge about these two gene groups could lead to establishment of a blueprint of the immune response and adaptation-related genes in the microgravity environment. Methods: Human peripheral blood cells were cultured in 1g (T flask) and modeled microgravity (MMG, rotating-wall vessel) for 24 and 72 hours. Cell samples were collected and subjected to gene array analysis using the Affymetrix HG_U95 array. Data was collected and subjected to a two-way analysis of variance. The genes related to immune and stress responses were analyzed. Results and Conclusions: HSP70 was up-regulated by more than two fold in microgravity culture, while HSP90 was significantly down-regulated. HSP70 is not typically expressed in all kinds of cells, but it is expressed at high levels in stress conditions. HSP70 participates in translation, protein translocation, proteolysis and protein folding, suppressing aggregation and reactivating denatured proteins. Increased serum HSP70 levels correlate with a better outcome for heat-stroke or severe trauma patients. At the same time, elevated serum levels of HSP70 have been detected in patients with peripheral or renal vascular disease. HSP90 has been identified in the cytosol, nucleus and endoplasmic reticulum, and exists in many tissue types. HSP90 associates with actin filaments in certain conditions and aids cell motility. The down-regulation of HSP90 could lead to deleterious effects in the lymphocytes, thereby contributing to suppressed immune function in microgravity. Interleukins such as IL 1 alpha, IL11 receptor chain alpha, IL7R, and IL4R were significantly down regulated in modeled microgravity. Further analysis of the genes involved in immune response at the protein level may provide a basis for prophylactic and countermeasure strategies to augment the human immune system for space exploration.

Sundaresan, Alamelu↗
NASA NTRS1997

Patent Foramen Ovale in Patients with Cerebral Infarction: A Transesophageal Echocradigraphy Study

Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P=.03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes me!litus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P=.08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P=.Ol). Conclusion: Although PFO was over-represented in patients with infarcts of uncertain cause in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

Petty, George W.↗
NASA NTRS2010

Particulate Emissions Hazards Associated with Fueling Heat Engines

All hydrocarbon- (HC-) fueled heat engine exhaust (tailpipe) emissions (<10 to 140 nm) contribute as health hazards, including emissions from transportation vehicles (e.g., aircraft) and other HC-fueled power systems. CO2 emissions are tracked, and when mapped, show outlines of major transportation routes and cities. Particulate pollution affects living tissue and is found to be detrimental to cardiovascular and respiratory systems where ultrafine particulates directly translocate to promote vascular system diseases potentially detectable as organic vapors. This paper discusses aviation emissions, fueling, and certification issues, including heat engine emissions hazards, detection at low levels and tracking of emissions, and alternate energy sources for general aviation.

Hendricks, Robert C.↗
NASA NTRS2017

VESsel GENeration Analysis (VESGEN): Innovative Vascular Mappings for Astronaut Exploration Health Risks and Human Terrestrial Medicine

Currently, astronauts face significant health risks in future long-duration exploration missions such as colonizing the Moon and traveling to Mars. Numerous risks include greatly increased radiation exposures beyond the low earth orbit (LEO) of the ISS, and visual and ocular impairments in response to microgravity environments. The cardiovascular system is a key mediator in human physiological responses to radiation and microgravity. Moreover, blood vessels are necessarily involved in the progression and treatment of vascular-dependent terrestrial diseases such as cancer, coronary vessel disease, wound-healing, reproductive disorders, and diabetes. NASA developed an innovative, globally requested beta-level software, VESsel GENeration Analysis (VESGEN) to map and quantify vascular remodeling for application to astronaut and terrestrial health challenges. VESGEN mappings of branching vascular trees and networks are based on a weighted multi-parametric analysis derived from vascular physiological branching rules. Complex vascular branching patterns are determined by biological signaling mechanisms together with the fluid mechanics of multi-phase laminar blood flow.

astronaut↗
NASA NTRS1980

Assessment of oxygen and carbogen therapy effect in Meniere's disease according to clinical and electroencephalographic data

The method of constructing fields on the basis of EEG data gives a quantitative characterization of bioelectrical activity. Fields of average rates of the change of potentials in healthy people have a well defined configuration, where the greatest rates are found in the occipital zones, lower in the frontal and parietal, and least in the temporal zones. In response to functional loads the form of the field remains the same because of a synchronous change in the average rates in both hemispheres of the cerebrum to the same extent. The configuration of the fields of background bioelectric activity of the cerebrum in people with Meniere's disease is not uniform. On the basis of this investigation, a clear correlation was found between the subjective sensations of patients during oxygen and carbogen therapy and the changes in the spatial characteristics of the field of potentials of the cerebrum. This correlation makes it possible to objectively identify the nature of the vascular disturbances in Meniere's disease, develop a pathogenetic treatment plan, and evaluate its effectiveness.

Boronoyev, A. B.↗
NASA NTRS1992

Ventilation-perfusion matching during exercise

In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

Non-NASA Center↗
NASA NTRS2005

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Non-NASA Center↗